Synthetic and systems biology for microbial production of commodity chemicals

The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we en...

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Published inNPJ systems biology and applications Vol. 2; no. 1; p. 16009
Main Authors Chubukov, Victor, Mukhopadhyay, Aindrila, Petzold, Christopher J, Keasling, Jay D, Martín, Héctor García
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.04.2016
Nature Publishing Group
Springer Nature
Subjects
631/553
631/553/552
Bioinformatics
Biomedical and Life Sciences
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Life Sciences
Review
review-article
synthetic biology
Systems Biology
Online AccessGet full text

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Abstract The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
AbstractList The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
ArticleNumber 16009
Author Chubukov, Victor
Martín, Héctor García
Keasling, Jay D
Mukhopadhyay, Aindrila
Petzold, Christopher J
Author_xml – sequence: 1
  givenname: Victor
  surname: Chubukov
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  organization: Joint BioEnergy Institute, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory
– sequence: 2
  givenname: Aindrila
  surname: Mukhopadhyay
  fullname: Mukhopadhyay, Aindrila
  organization: Joint BioEnergy Institute, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory
– sequence: 3
  givenname: Christopher J
  surname: Petzold
  fullname: Petzold, Christopher J
  organization: Joint BioEnergy Institute, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory
– sequence: 4
  givenname: Jay D
  surname: Keasling
  fullname: Keasling, Jay D
  organization: Joint BioEnergy Institute, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Department of Chemical & Biomolecular Engineering, University of California, Department of Bioengineering, University of California
– sequence: 5
  givenname: Héctor García
  surname: Martín
  fullname: Martín, Héctor García
  email: hgmartin@lbl.gov
  organization: Joint BioEnergy Institute, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28725470$$D View this record in MEDLINE/PubMed
https://www.osti.gov/servlets/purl/1378752$$D View this record in Osti.gov
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Snippet The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical...
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631/553/552
Bioinformatics
Biomedical and Life Sciences
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Life Sciences
Review
review-article
synthetic biology
Systems Biology
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Title Synthetic and systems biology for microbial production of commodity chemicals
URI https://link.springer.com/article/10.1038/npjsba.2016.9
https://www.ncbi.nlm.nih.gov/pubmed/28725470
https://www.proquest.com/docview/1787469330
https://www.proquest.com/docview/1921133109
https://www.osti.gov/servlets/purl/1378752
https://pubmed.ncbi.nlm.nih.gov/PMC5516863
Volume 2
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